In the last decades the Common Agricultural Policy has evolved towards a less intensive approach based in a multifunctional agriculture respectful with the environment. At the same time, following the enacting of the Water Framework Directive in 2000, water policies and management regimes are also evolving towards more integrated water management with an active stakeholders’ involvement. In this context, the aim of this paper is to analyze the impact of water conservation policies and agricultural policies (Cross-Compliance: Nitrates Directive) in the Upper Guadiana River basin (Spain), where intensive irrigated agriculture resulted in the overexploitation of the Western La Mancha aquifer and the subsequent degradation of the highly valuable wetlands, and in an important nitrates’ pollution. Focus is made on farmers’ vulnerability to these policies and the synergies between them. The methodology combines qualitative and quantitative aspects defined by the integration of an economic and an agronomic model (CropSyst), and a vulnerability analysis. The economic model (mathematical programming model) simulates farmers’ behaviour facing different policy options. The results of the economic model are used as an input for the analysis of farms’ vulnerability based on farm income indicators, through the elaboration of a vulnerable farms classification tree using CART (Classification and Regression Trees). The results of the model show that farm income is more sensitive to water use limitations than to nitrogen restrictions. Farm size and Water Authority’s policy enforcement capacity are key variables in determining farmers’ vulnerability, being small and legal farms the most vulnerable ones.